Background: Dyslipidemia affects more than 70% of children and adolescents with juvenile systemic lupus erythematosus (JSLE), increasing their risk of developing cardiovascular disease. In adult patients, antimalarials like hydroxychloroquine (HCQ) have beneficial effects on dyslipidemia. However, the role of HCQ concentrations in this context is lacking. Therefore, the objective of the present study was to evaluate if HCQ blood levels have an impact on the lipoprotein profile in JSLE patients.

Objectives: To evaluate the influence and impact of hydroxychloroquine (HCQ) blood levels on the lipoprotein profile in patients with juvenile systemic lupus erythematosus (JSLE).

Methods: Cross-sectional study that included eighty-six JSLE patients on a stable dose of HCQ for at least 6 months were included. HCQ did not to exceed 5 mg/kg/day (real body weight). Blood HCQ levels, lipid profile [fasting total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG)], and JSLE parameters at study inclusion were assessed. HCQ blood levels were measured by liquid chromatography-tandem mass spectrometry. Serum lipids were measured using commercial kits and classified as adequate, borderline, and risk levels. Receiver operating characteristic (ROC) curves were used to determine HCQ concentrations associated with the risk lipoprotein profile.

Results: The median age of JSLE patients was 17 years, with 84.9% being female. At baseline, 25 (29.1%) had borderline/high TC levels, 39 (45.3%) had borderline/low HDL levels, 17 (19.8%) had borderline/high LDL levels, and 37 (43%) had borderline/high TG levels. ROC curve analysis determined that HCQ levels <937 ng/mL were associated with low HDL levels in patients under prednisone with a sensitivity of 73.9% and specificity of 61.5% (OR=4.12 95% CI 1.23-13.77, p=0.021). Demographic characteristics (age, sex, BMI), treatment (immunosuppressive drugs, glucocorticoid use/current and cumulative dose), and disease parameters (SLEDAI-2K and SLICC/ACR damage index) were similar between patients with low HCQ levels (<937 ng/mL) versus adequate (≥937 ng/mL; p>0.05). Mean baseline HDL levels were significantly lower in patients with low HCQ blood levels compared to those with adequate levels (44.8 ± 12.3 vs. 53.3 ± 15.9 mg/dL, p=0.007), and a positive correlation was observed between HDL and HCQ blood levels (r=+0.239, p=0.029). Multiple logistic regression analysis showed that HCQ blood level <937 ng/mL (OR 3.79, 95% CI 1.41-10.21, p=0.008) and borderline/high TG (OR 2.929, 95% CI 1.11-7.66, p=0.029) were independently associated with low HDL.

Conclusion: HCQ blood levels below 937 ng/mL are significantly associated with low HDL levels in JSLE patients. Maintaining adequate HCQ levels may help manage dyslipidemia in this population. Further research with larger cohorts is needed to confirm these findings and understand the long-term effects of HCQ on lipid profiles in JSLE patients.

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Acknowledgements: I would like to express my deepest gratitude to the Rheumatology Service of the University of São Paulo (USP) for their invaluable support and guidance throughout this work. A special thanks to Dr. Nadia Aikawa, my thesis advisor, whose expertise, mentorship, and encouragement were fundamental in the development and completion of this study. Her dedication to academic excellence and patient care continues to inspire me and countless others in the field of rheumatology.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.